{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:59:55Z","timestamp":1793177995592,"version":"4.5.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,7,27]]},"abstract":"\n The programmed death-1 (PD-1) costimulatory receptor inhibits T and B cell responses and plays a crucial role in peripheral tolerance. PD-1 has recently been shown to inhibit T cell responses during chronic viral infections such as HIV. In this study, we examined the role of PD-1 in infection with\n Mycobacterium tuberculosis<\/jats:italic>\n , a common co-infection with HIV. PD-1\u2013deficient mice showed dramatically reduced survival compared with wild-type mice. The lungs of the PD-1\n \u2212\/\u2212<\/jats:sup>\n mice showed uncontrolled bacterial proliferation and focal necrotic areas with predominantly neutrophilic infiltrates, but a lower number of infiltrating T and B cells. Proinflammatory cytokines, such as TNF-\u03b1, IL-1, and especially IL-6 and IL-17 were significantly increased in the lung and sera of infected PD-1\n \u2212\/\u2212<\/jats:sup>\n mice, consistent with an aberrant inflammation. Microarray analysis of the lungs infected with\n M. tuberculosis<\/jats:italic>\n showed dramatic differences between PD-1\n \u2212\/\u2212<\/jats:sup>\n and control mice. Using high-stringency analysis criteria (changes of twofold or greater), 367 transcripts of genes were differentially expressed between infected PD-1\n \u2212\/\u2212<\/jats:sup>\n and wild-type mice, resulting in profoundly altered inflammatory responses with implications for both innate and adaptive immunity. Overall, our studies show that the PD-1 pathway is required to control excessive inflammatory responses after\n M. tuberculosis<\/jats:italic>\n infection in the lungs.\n <\/jats:p>","DOI":"10.1073\/pnas.1007394107","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T23:40:19Z","timestamp":1278978019000},"page":"13402-13407","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":307,"title":["Programmed death-1 (PD-1)\u2013deficient mice are extraordinarily sensitive to tuberculosis"],"prefix":"10.1073","volume":"107","author":[{"given":"Eszter","family":"L\u00e1z\u00e1r-Moln\u00e1r","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology,"},{"name":"Howard Hughes Medical 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